Modulation of gene expression using localization domains

Abstract

Methods and compositions for regulating gene expression are provided. In particular, methods and compositions comprising localization domains, and fusions of localization domains with DNA binding domains and, optionally regulatory domains, are provided.

1 . A polynucleotide encoding a fusion polypeptide, wherein the polypeptide comprises: 
 a) a localization domain, wherein the localization domain is a chromodomain or is a localization domain from a protein selected from the group consisting of methylated DNA-binding proteins (MBDs), DNA-N-methyl transferases (dNMTs) and MBD-like proteins; and    b) a DNA binding domain that is heterologous to the localization domain, or functional fragment thereof.    
     
     
         2 . The polynucleotide of  claim 1 , wherein the DNA-binding domain is a zinc finger DNA binding domain.  
     
     
         3 . The polynucleotide of  claim 1 , wherein the localization domain is a methyl CpG binding domain.  
     
     
         4 . The polynucleotide of  claim 3 , wherein the methyl CpG binding domain is from a gene involved in a disease state selected from the group consisting of ICF syndrome, Rett syndrome and Fragile X syndrome.  
     
     
         5 . The polynucleotide of  claim 1 , wherein the protein from which the localization domain is obtained is selected from the group consisting of dMBD-like and dMBD-likeΔ.  
     
     
         6 . The polynucleotide of  claim 1 , wherein the fusion polypeptide further comprises: 
 c) a regulatory domain or functional fragment thereof.    
     
     
         7 . The polynucleotide of  claim 6 , wherein the regulatory domain is an activation domain.  
     
     
         8 . The polynucleotide of  claim 7 , wherein the activation domain comprises VP-16, p65 or functional fragments thereof.  
     
     
         9 . The polynucleotide of  claim 6 , wherein the regulatory domain is a repression domain.  
     
     
         10 . A cell comprising the polynucleotide of  claim 1 .  
     
     
         11 . The cell of  claim 10 , wherein the cell is a plant cell.  
     
     
         12 . The cell of  claim 10 , wherein the cell is an animal cell.